Lipid Nanoparticles: Versatile, Sophisticated Drug Delivery Systems  

Since the discovery of the first-generation liposomes in the 1960s, lipid nanoparticles (LNPs) have evolved tremendously. The key application of LNPs as therapeutic vehicles is in the pharmaceutical industry, although they serve purpose in other fields such as medical imaging, cosmetics, nutrition, and agriculture, albeit on a smaller scale.

Lipid nanoparticles have been widely used in the pharmaceutical industry for decades. Compared with other gene and vaccine delivery systems, they are easier to manufacture, less immunogenic, and can carry larger payloads – making them successful and efficient carriers for various kinds of therapeutics, including small molecules, proteins, and nucleic acids.

Recently, lipid nanoparticles were propelled into the global spotlight for their role in two approved COVID mRNA vaccines, effectively aiding accurate mRNA delivery, which sees them as a cutting-edge technology in vaccine platforms. Apart from mRNA therapeutics, lipid nanoparticles can play a key role in other disease areas. In fact, a number of lipid nanoparticles are already approved for delivering treatments for a variety of diseases (Figure 1). Here, we briefly explore the use of lipid nanoparticles in antitumor therapeutics.

Applications of Lipid Nanoparticles in Cancer Therapy

The CAS Content Collection™ has allowed us to review the distribution of treatment areas that use  LNP formulations (Figure 2). We have seen that antitumor therapeutic effects comprise the biggest portion of LNP drug use (46%), indicating their prominent role in this area. The largest single use of antitumor LNP formulations is seen in breast cancer (>25%), followed by ovarian cancer and lung cancer (both 10%).  

Lipid nanoparticles are associated with multiple therapeutic benefits that make them suitable for drug delivery in cancer treatment:  

LNPs have also been shown to improve the efficacy of cancer therapies via what is known as an enhanced permeability and retention (EPR) effect. LNPs can readily pass through tumor blood vessels, owing to their increased permeability resulting from rapid, yet defective, angiogenesis. This allows selective accumulation of LNPs in tumors when they are administered intravenously via direct injection, though data varies for different administration routes. Furthermore, dysfunctional lymphatic drainage in tumors improves LNP retention; the accumulation of LNPs allows the selective release of antitumor agents inside tumor cells.  

To better understand the applicability of LNPs across different therapies, the CAS Content Collection™ was employed to correlate different LNP formulation processes with the therapies that they may be applied to: immunoliposomes and stealth liposomes were found to be the most ubiquitous LNP types for antitumor therapy.  

One example of a highly effective stealth liposome cancer therapy is DOXIL^® (doxorubicin HCl liposome injection), the earliest approved liposomal drug developed for the management of advanced ovarian cancer, multiple myeloma, and HIV-associated Kaposi’s sarcoma. The LNPs used in DOXIL^® employ the EPR effect to overcome the cardiotoxic properties of the potent anticancer agent, doxorubicin, while sterically stabilized nanoparticles extend circulation time in human plasma.

With regards to current and future research, a number of Phase I/II clinical trials are currently investigating LNP formulations as cancer immunotherapy targets in an array of solid tumors, including melanoma, adult glioblastoma, gastrointestinal cancer, and genitourinary cancer, to name a few – underlining the broad clinical use of these therapies.  

Stimuli-responsive liposomes are another approach being investigated to further enhance drug delivery in tumors, where they are designed to be released under certain physicochemical or biochemical stimuli. Examples include doxorubicin (stimuli: temperature/pH), 5-fluorouracil (stimulus: magnetic field), and AMD3100 (stimulus: laser irradiation).

The Future of Lipid Nanoparticles in the Emerging Field of Nanomedicine

The field of nanomedicine has shown remarkable progress as a modern drug therapy with broad clinical applications beyond cancer. Nanomedicine has helped to improve the effectiveness, selectivity, and biodistribution of conventional drug carrier systems while reducing their limitations.  

The use of lipid nanoparticles in medicine is likely to expand, and holds great promise in genetic medicine where gene editing, vaccine development, and immuno-oncology rely on the ability to efficiently deliver nucleic acids into cells. More sophisticated and multifunctional nanocarrier designs are being developed to address the needs of personalized medicines, meaning successful drug delivery, regardless of a patient’s biological barriers related to age, disease status, and comorbidities.  

With continued development, lipid nanoparticles can be recognized as one of the most advantageous and promising areas in modern nanotechnology.

Tenchov R, et al. Lipid nanoparticles - From liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano. 2021 Jun 28. doi: 10.1021/acsnano.1c04996. Online ahead of print.